Polymerizable compounds with at least one conjugated unsaturated group are widely used as basic chemicals. Examples are acrylic monomers, in particular acrylic acid and methacrylic acid. They are mostly used for the synthesis of polymers. In recent times such polymerizable compounds have been used in medicine.
Polymerizable compounds with at least one conjugated unsaturated group are also known to be used for forming biodegradable materials. In WO 01/92584 a matrix material is disclosed which is formed by nucleophilic addition reaction to conjugated unsaturated groups.
WO 00/44808 also discloses a polymeric biomaterial formed by nucleophilic addition reaction to conjugated unsaturated groups. The obtained hydrogels may be used for example as glues or sealants and as scaffolds for tissue engineering and wound healing applications.
During the manufacture, transport and storage of these polymerizable compounds with at least one conjugated unsaturated group, the so-called “runaway” polymerization has to be avoided, since this leads not only to quality loss of the monomer but also to safety problems. Especially when used in medicine such compounds have to fulfill purity requirements, since polymerization would impede stoichiometry of the nucleophilic addition reaction and cause premature gelation of a product. The research of past decades on the inhibition of polymerization of for example acrylic monomers has produced many usable inhibitors to prevent the radical polymerization.
An example of a powerful inhibitor is a methyl ether of hydroquinone (MEHQ), which is usually present in acrylic acid at a concentration of approximately 200 ppm (S. Schulze, H. Vogel, Chem. Eng. Technol. 21, 829-836 (1998)). Said inhibitor works only in the presence of oxygen. Therefore MEHQ is not suitable for compositions which are to be used in medicine. Oxygen could impair the longterm stability of components of these compositions, e.g. peroxides could be formed in poly(ethylene glycol), and should therefore not be present in such compositions.
Another inhibitor which is industrially used to inhibit polymerization of said polymerizable compounds is phenothiazine (PTZ). In contrast to MEHQ, PTZ is also a good inhibitor in the absence of oxygen (Levy, J. Polymer Science: Part A: Polymer Chemistry, Vol 30, 569-576 (1992)). Said compound is known for its insecticidal, fungicidal, antibacterial and anthelmintic properties. Due to its widespread use in animals and man many adverse reactions are known encompassing effects on blood elements, neuromuscular problems and photosensitization (Mitchell, S. C., the toxicity of phenothiazine, Drug Metabolism and Drug Interactions, 11, 204-235 (1994)). Due to said adverse reaction phenothiazine-based inhibitors should not be used in compositions which are to be used in medicine.
Methylene blue is a well known dye. It is used as dye in medicine and is known to be biocompatible. For example U.S. Pat. No. 7,009,034 B2 discloses biocompatible crosslinked polymers which may contain visualization agents to improve their visibility during surgical procedures. A possible visualization agent is methylene blue.
Methylene blue is also used in the process for preparing methacrylic compounds. GB 942318 discloses a process for preparing methacrylamide and/or sulphuric acid derivative. The reaction may be carried out in the presence of methylene blue. U.S. Pat. No. 4,021,310 discloses a method for inhibiting the polymerization of acrylic acid or acrylic esters during the distillation for separating or purifying the acrylic acid obtained by the vapour phase catalytic oxidation of propylene or acrolein. Said method is carried out in the presence of molecular oxygen, a copper compound and a further compound which may be methylene blue.
DE 215 699 discloses a dental composition which is curable by light comprising an acrylate compound, an initiator compound as well as a dye. The dye is added to produce singlet oxygen. As possible dye methylene blue is mentioned.
By “conjugated unsaturated group” the alternation of carbon-carbon, carbon-heteroatom or heteroatom-heteroatom multiple bonds with single bonds is meant.
By “polymerizable compound” is meant that said compound can undergo a polymerization reaction.